Hollow microparticles

Abstract

The invention provides a process for making hollow microparticles. The process comprises providing a dispersion having a continuous aqueous phase and a discontinuous organic phase and polymerising a monomer in the dispersion to form hollow polymeric microparticles. The continuous aqueous phase of the dispersion comprises a stabiliser and the discontinuous organic phase of the dispersion comprises the monomer and an organic liquid. The monomer has two or more polymerisable groups per molecule. Prior to the step of polymerising the monomer, the discontinuous organic phase does not contain a polymer.

1 . A process for making hollow microparticles comprising:
 a) providing a dispersion having a continuous aqueous phase and a discontinuous organic phase, wherein the continuous aqueous phase comprises a stabiliser and the discontinuous organic phase comprises a monomer having two or more polymerisable groups per molecule and an organic liquid; and   b) polymerising the monomer in the dispersion to form hollow polymeric microparticles;   
     wherein, prior to step b) the discontinuous organic phase does not contain a polymer. 
   
   
       2 . The process of  claim 1  wherein the monomer is selected so that the polymer of the microparticles is capable of reacting with a chemical to which the microparticles are exposed in order to release a substance encapsulated in the hollow polymeric microparticles. 
   
   
       3 . The process of  claim 2  wherein the monomer comprises a cleavable linkage between two of the polymerisable groups, such that the polymer of the microparticles is capable of degrading in order to release the substance. 
   
   
       4 . The process of  claim 3  wherein the cleavable linkage is a hydrolysable linkage and the polymer is capable of hydrolysing in order to release the substance. 
   
   
       5 . The process of any one of  claims 1  to  3  wherein the cleavable linkage is selected from the group consisting of a disulfide, an ester, an anhydride, an orthoester and an acetal. 
   
   
       6 . The process of any one of  claims 1  to  5  wherein the discontinuous organic phase additionally comprises a second monomer which is capable of copolymerising in step b) with the monomer having two or more polymerisable groups per molecule. 
   
   
       7 . The process of  claim 6  wherein the monomer having two or more polymerisable groups per molecule comprises a degradable non-hydrolysable linking group and the second monomer comprises a hydrolysable group, whereby a shell of the hollow microparticles comprises a copolymer comprising degradable non-hydrolysable crosslinks and also comprising hydrolysable groups. 
   
   
       8 . The process of  claim 7  additionally comprising at least partially hydrolysing the hydrolysable groups of the copolymer so as to render the surface of the microparticles hydrophilic. 
   
   
       9 . The process of any one of  claims 1  to  8  wherein the monomer having two or more polymerisable groups per molecule or the second monomer, if present, or both, comprises a hydrolysable group, such that hydrolysis of the hydrolysable group in the polymer of the microparticles alters the polarity of said polymer without causing backbone chain breaking of the polymer. 
   
   
       10 . The process of any one of  claims 1  to  9  wherein the stabiliser is polymeric. 
   
   
       11 . The process of any one of  claims 1  to  10  wherein the stabiliser is a thickener. 
   
   
       12 . The process of any one of  claims 1  to  11  wherein the organic liquid is a non-solvent for the polymer. 
   
   
       13 . The process of any one of  claims 1  to  12  wherein the organic liquid is a solvent for the monomer having two or more polymerisable groups per molecule and for the second monomer, if present. 
   
   
       14 . The process of any one of  claims 1  to  13  wherein the discontinuous organic phase comprises a thermal initiator and step b) comprises heating the dispersion so as to polymerise the monomer(s). 
   
   
       15 . The process of any one of  claims 1  to  14  wherein the discontinuous organic phase comprises a photoinitiator and step b) comprises irradiating the dispersion with radiation having a wavelength and intensity sufficient to polymerise the monomer(s). 
   
   
       16 . The process of any one of  claims 1  to  15  additionally comprising:
 c) loading a substance into the interior region of the hollow microparticles to form loaded microparticles.   
   
   
       17 . The process of  claim 16  wherein the substance is a drug. 
   
   
       18 . The process of  claim 16  or  17  wherein the substance is usable in the treatment of cancer. 
   
   
       19 . The process of any one of  claims 16  to  18  wherein neutron bombardment of the substance generates a n-emitter. 
   
   
       20 . Hollow microparticles made by the process of any one of  claims 1  to  19 . 
   
   
       21 . A method of treating a condition in a patient comprising administering to said patient a therapeutically effective quantity of microparticles according to  claim 20 , wherein a substance indicated for treatment of said condition is located in the interior region of the microparticles. 
   
   
       22 . A method of treating cancer in a patient comprising:
 exposing a therapeutic quantity of hollow polymeric microparticles according to  claim 20  to neutrons from a neutron source, wherein a substance in the interior region of the hollow polymeric microparticles is such that the exposure generates a β-emitter; and   administering the therapeutic quantity of hollow microparticles to the patient.   
   
   
       23 . Use of hollow polymeric microparticles according to  claim 20  for the manufacture of a medicament for the treatment of cancer. 
   
   
       24 . A method for releasing a substance from a core of a polymeric microparticle according to  claim 20 , said core containing the substance, said method comprising exposing said polymeric microparticle to a reagent which causes cleavage of crosslinks of a polymeric shell of the microparticle so as to cause said microparticle to release said substance. 
   
   
       25 . The method of  claim 24  wherein said crosslinks are hydrolysable crosslinks and said reagent is a hydrolytic reagent. 
   
   
       26 . The method of  claim 25  wherein said crosslinks are disulfide crosslinks and said reagent comprises a thiol.